There is good evidence to support screening for alcohol dependency and alcohol use disorders when using standard screening tools in practice. For the family physician, the diagnosis of alcoholism often depends on clues from the history and physical examination (Box 49-1). Possible clues may include a history of driving under the influence (DUI) or an MVC; history of repetitive trauma; new-onset hypertension, gastritis, or pancreatitis; other, otherwise unexplained liver disease (AST > ALT); presence of depression; recent loss of employment or separation from family; unexplained tremor; upper gastrointestinal (GI) bleeding; recent falls or accidents; and a history of family or marital violence.

Box 49-1 Screening Clues for Alcoholism

“Driving under the influence” (DUI) arrest

Domestic violence

Unexplained trauma

The four CAGE questions (cut down, annoyed, guilty, eye opener) are adequate for screening purposes (Box 49-2), derived from the longer Michigan Alcoholism Screening Test (MAST) questions (see eTable 49-1 online) (Hays and Spickard, 1987; Powers and Spikard, 1984). Two positive responses are considered a positive screen and indicate that further assessment is warranted. An important point is that family physicians should not assume that someone does not have an alcohol use disorder when that person answers negatively to questions about drinking. If such patients do not use alcohol at all, it may indicate that they had to quit because they had problems with alcohol. Given the prevalence of alcohol use disorders, it is recommended that the CAGE questions be applied to all patients older than 18 years. Another brief set of screening questions is the TWEAK questionnaire: tolerance, worries, eye openers, amnesia, and cut down (Box 49-3).

Box 49-2 Brief Screening Questions for Alcohol Use

CAGE^∗

1. Have you ever felt you should cut down, on your drinking?

2. Have people annoyed you by criticizing your drinking?

3. Have you ever felt bad or guilty about your drinking?

4. Have you ever had a drink first thing in the morning to steady your nerves or to get rid of a hangover (eye opener)?

Scoring: Item responses on the CAGE are scored 0 for “no” and 1 for “yes” answers, with a higher score an indication of alcohol problems. A total score of 2 or greater is considered clinically significant.

The normal cutoff for the CAGE is two positive answers; however, the Consensus Panel recommends that the primary care clinicians lower the threshold to one positive answer to cast a wider net and identify more patients who may have substance abuse disorders. A number of other screening tools are available.

^∗ Ewing JA. Detecting alcoholism: the CAGE questionnaire. JAMA 1984;252:1905-1907.

^† Brown RL, Rounds LA. Conjoint screening questionnaires for alcohol and drug abuse. Wis Med J 1995;94:135-140.

Box 49-3 TWEAK Screening For Alcohol Use

TWEAK is a five-item scale developed originally to screen for risk drinking during pregnancy.

Longer screening questionnaires include the MAST and the Alcohol Use Disorders Test (AUDIT: see eTable 49-2 online) (Saunders et al., 1993). Both are considered higher in predictive value but more difficult to administer. Age-specific and population-specific survey tools are also available, including the Geriatric Alcoholism Screen and an adolescent alcoholism inventory. The 10-item Core questionnaire includes three questions on alcohol consumption (the AUDIT-C) and seven on the impact of alcohol use. The AUDIT has been shown to have good sensitivity and specificity in medical and general populations and has recently been useful for screening patients with major psychiatric disorders and as an assessment instrument for patients seeking treatment for alcohol use disorders (Cassidy et al., 2008; Donovan et al., 2006). The AUDIT-C provides an efficient standardized method for assessing the quantity and frequency of alcohol use and accounts for much of the test’s discriminative power in medical populations (Rodriguez-Marros and Santamarina, 2007).

Biologic Markers

Key Points

• The MCV is higher than 100 fL.

• The AST level is higher than the ALT level.

• There is a positive response to CDT level.

• Five drinks daily for 2 weeks elevates GGT in most people.

• Using GGT and CDT in combination increases sensitivity over either marker alone by 20% without compromising specificity.

Diagnostic clues from the laboratory include a complete blood count (CBC) with an elevated mean cell volume, elevated γ-glutamyltransferase (GGT), aspartate transaminase (AST) level higher than alanine transaminase (ALT), unexplained leukopenia or thrombocytopenia, and positive response to the carbohydrate-deficient transferrin (CDT) level (Borg et al., 1992). It is estimated that 5 drinks/day for two weeks will yield an elevated GGT in most people (USDHHS, SAMSHA, 2006). Using CDT and GGT together increases sensitivity by 20% of either marker alone without compromising specificity (Hitela et al., 2006). Dose-response relationships are not well established, making it difficult to use these tests as a direct quantifier for alcohol consumption (Allen et al., 2004).

Interview Questions

Guidelines for interviewing adolescents about alcohol have been reviewed (Speraw and Rogers, 1998). An atmosphere of trust and privacy must be conveyed (parents should be excluded). The questioning should be gradually moved from nonthreatening areas about general lifestyle to more specific questions about medications to questions about alcohol use. Standard interview questions for alcohol abuse include quantity of consumption; frequency of consumption; preference of alcoholic beverages; age at onset of drinking; attempts to cut down or quit; time of most recent drink; adverse sequelae related to drinking (or stopping drinking); and pattern of drinking (continuous, daily drinking, binge pattern). Quantity questions can classify binge drinking as never, less than one, one to three, three to five, and more than five per month. Vague or evasive answers, as well as rationalizations, should be “red flags.” Patients can also be asked how much alcohol they purchase and how often. It is important to elicit specific, concrete information and not become derailed by certain responses.

A family history of alcohol problems must be detailed because it is a major predictive variable. When a clinician receives the answer that the patient does not drink at all, the line of questioning should still be pursued to determine whether cessation was problem based. Once it has been established that the person has a history of binge drinking or continuous daily drinking, follow-up questions are in order. These questions may include role impairment, family concerns, amnesia, self-concern, and hangovers to determine the patient’s sentiments about alcohol consumption.

Detailed Assessment

Once it has been established that the patient has problems with alcohol, more detailed assessment is in order. The history should then be focused on the known harmful consequences of alcohol abuse and dependency as related to the patient’s history. (For a list of complications, see Woodard, 2009). Major disorders include Wernicke’s encephalopathy, withdrawal seizures, cerebellar disease, peripheral neuropathy, cardiomyopathy, cirrhosis, pancreatitis, gastritis, bone marrow suppression, and aseptic necrosis of the hip. A careful history should include an assessment of tolerance and withdrawal symptoms, including shakes, hallucinosis, seizures, and delirium tremens (DTs). The time of the last drink and quantification of daily drinking are prerequisites. A history of stage 2 to 4 withdrawal with or without a history of serious medical complications is in itself justification for acute care hospitalization. Alcohol withdrawal often includes anxiety, nausea, vomiting, diarrhea, tremors, and elevated pulse and blood pressure (BP). A history of blackout or amnesic episodes while drinking must also be elicited. A history of family, social, legal, and occupational complications should be obtained as part of the diagnosis of alcoholism.

A psychiatric evaluation is key in the assessment for alcohol abuse. Screening tools such as the Beck Depression Inventory can help identify underlying depression. Assessment of suicidal ideation must be documented, because alcoholics are at much greater risk for suicide-related deaths. The Mini–Mental Status Examination (MMSE) can be useful for assessing possible dementia or delirium and pointing to the need for more extensive neuropsychiatric testing (see Chapter 48). Cognitive damage may be a factor in denial, a trait that characterizes many patients with known alcohol dependency. A sexual history should be included, with attention to multiple partners and human immunodeficiency virus (HIV) risk assessment. A history of comorbid polysubstance abuse and intravenous (IV) drug use should also be sought. Cough hemoptysis, night sweats, fever, and weight loss suggest the need to investigate for tuberculosis.

Physical Assessment

The physical examination should pay close attention to vital signs. Elevated BP, pulse, or respiration can be a clue to the severity of alcohol withdrawal. The smell of ethanol on the breath will point to acute intoxication; the comorbid “dry mouth” may then be a local effect and not related to dehydration. Skin changes can be seen in alcoholics and may include rhinophyma, red swollen facies, and porphyria cutanea tarda. A thorough neurologic examination is in order, including cranial nerves, extraocular movements, gait, and cerebellar signs, as well as a sensory assessment of the lower extremities. Ataxia and nystagmus can be clues to possible intoxication or Wernicke’s encephalopathy. Percussion and palpation of the liver are important in alcoholism. Examination of the extremities can include visualization of Dupuytren’s contractures and palmar erythema. An irregular heart rhythm suggests atrial fibrillation, or “holiday heart.”

In women, diagnosis of pregnancy should also be excluded (see Alcohol Use Disorder in Women). Alcoholism in pregnancy has severe perinatal effects. Cardiovascular, liver, GI, neurologic, and other sequelae of alcohol and other drugs of abuse have been reviewed (Gordis, 2003). Alcohol abuse is frequently associated with hypertension.

KEY TREATMENT

Evidence on the effectiveness of counseling to reduce alcohol consumption during pregnancy is limited; however, studies in the general adult population show that behavioral counseling interventions are effective among women of childbearing age. The benefits of behavioral counseling interventions to reduce alcohol misuse by adults outweigh any potential harm (USPSTF, USDHHS, 2006) (SOR: B).

Management

Alcohol Intoxication

Key Points

• Naive alcohol users are impaired at lower levels.

• Always give thiamine to alcoholic patients.

• Urine toxicology is frequently helpful for concomitant drug use.

Alcohol intoxication is frequently seen as a component of trauma, domestic violence, or suicide attempts (McGinnis and Foege, 1993). The degree of intoxication is determined by the amount of alcohol ingested, the duration of the ingestion, and the patient’s tolerance, if any, for the alcohol. Subtle effects occur at levels of 20 mg/dL and include mild euphoria, mild impairment of coordination, and mood alterations. At 80 to 100 mg/dL, delayed reaction times and slurred speech may be noted. This 80-mg/dL level is generally accepted as an unsafe level for motor vehicle operation. Between 100 and 200 mg/dL, ataxia, grossly slurred speech, and incoordination occur. As the level climbs to 300 mg/dL, the ataxia becomes more marked, and drowsiness, lethargy, and vomiting may occur. In naive drinkers, levels above 400 mg/dL are associated with coma, respiratory depression, hypothermia, and death from central nervous system (CNS) depression, loss of airway integrity, or pulmonary aspiration. Chronic alcoholics will have different tolerance responses than those just listed and may be in severe withdrawal at substantial levels.

Alcohol-induced coma can be managed by protecting the airway and performing basic resuscitation, if necessary. The patient should be placed in a warm protective environment, with careful monitoring of vital signs. Gastric emptying is rarely helpful because of the rapid absorption of alcohol, but it may be considered if the ingestion has occurred within 60 minutes. Alcohol is eliminated mostly by hepatic metabolism, which follows zero-order kinetics. The rate does not change with changes in the alcohol blood level. Fructose can enhance elimination but is not typically used. In extreme cases, hemodialysis may be effective in reducing the level quickly. Activated charcoal does not efficiently absorb ethanol but may be given if other toxins have been ingested (Mayo-Smith, 2009).

Thiamine and glucose should always be administered, because chronic alcoholism is associated with hypoglycemia and thiamine deficient states such as Wernicke’s encephalopathy (mental confusion, cranial nerve palsies, ataxia). Thiamine should be given immediately before or with glucose to prevent hypoglycemia because glucose is metabolized with the enzyme thiamine pyrophosphorylase. The physician should look for additional drug use in all patients because the effects of other drugs may be obscured by the obvious alcohol intoxication (Mayo-Smith, 2009). A urine toxicology screen may be positive for concomitant intoxicants.

Overview of Alcoholism Treatment

Alcoholics who are actively drinking are among the highest cost users of medical services in the United States. Several studies have documented that alcohol treatment has beneficial effects on health care expenditures, primarily as a result of decreased health care use by alcoholics and their families. A Harvard Study compared 587 lifesaving interventions and ranked all substance abuse interventions, including treatment of alcoholism, in the top 10% (Tengs et al., 1995).

Physicians interface with the medical or behavioral effects of alcoholism when patients deteriorate to the point of trauma, end-organ damage, or behavioral impairment. As with other chronic disorders, alcoholism is slow but progressive. As the disease progresses, the ability to control drinking diminishes, which distinguishes an alcoholic from a nonalcoholic. Many physicians view detoxification as the treatment of this disorder, which is similar to giving diabetics one injection of insulin to control their diabetes. It treats the immediate problem but does little to address the chronic disorder in 1 week or 1 month. Although the goal for an alcoholic is complete abstinence from alcohol, the norm is alcohol consumption in increasing amounts. The family physician can view intermittent periods of abstinence or reductions in alcohol consumption as progress in treatment of the disease and encourage further efforts. Relapse must be evaluated carefully, and keys to change can open the door to further reductions or ongoing abstinence.

The American Society of Addiction Medicine (ASAM) has developed patient placement criteria (PPC) to better guide treatment of alcoholism.(Mee-Lee et al., 2001). The PPC can help to assign the appropriate level of care for detoxification and subsequent rehabilitation of those with alcohol use disorders. The ASAM criteria reflect a consensus of expert opinion for adolescents and adults in treatment. Levels of care are differentiated by three criteria: (1) degree of direct medical management provided; (2) degree of structure, safety, and security provided; and (3) degree of treatment intensity provided. The current criteria are under revision since 2007. Special populations who need consideration include pregnant and nursing women; adolescents; older adults; HIV-positive patients; patients with neurologic, cardiovascular, hepatic, or renal disorders; patients with psychiatric comorbidities; and persons in criminal justice settings (Wright et al., 2009).

Detoxification

The alcohol withdrawal syndrome is a somewhat predicable series of events that have a temporal relationship to the use, decrease in intake, or cessation of alcohol consumption. Alcohol withdrawal may occur in a patient who has a reduction in alcohol intake from a previously significant level or an absolute absence of alcohol. The pharmacology of alcohol and its subsequent metabolism is well known and follows zero-order kinetics, primarily through the liver and cytochrome pathways (Mayo-Smith, 2009).

Patients with mild to moderate alcohol withdrawal symptoms and no serious psychiatric or medical comorbidities can be safely treated in the outpatient setting (Asplund et al., 2004). The severity of these symptoms varies greatly among individuals, but in a majority, they are mild and transient, passing within 1 or 2 days (Driessen et al., 2005; Mayo-Smith, 2009). Westerling and colleagues (2006) developed a scale to predict severity of alcohol withdrawal.

The signs and symptoms of alcohol withdrawal vary individually but tend to be repetitive in the same person. Most alcoholics who withdraw from alcohol experience minimal symptoms, such as sleep disturbance or anxiety. A small number may have tremulousness, agitation, diaphoresis, and cognitive impairment. The tremors or shakes typically begin 12 to 14 hours after a period of heavy drinking and are usually noted in the early morning. Tremulousness may be accompanied by alcoholic hallucinosis, a misperception of objects in the patient’s sensory arena. Other symptoms of withdrawal include nausea, vomiting, poor oral intake, sweats, and anxiety. Seizures during alcohol withdrawal tend to occur as one isolated seizure or a brief cluster of seizures. Seizures are frequently preceded by tremors and tend to recur in a similar pattern in the same patient. Seizures may be the initial manifestation of alcohol withdrawal. Seizure activity is most common 24 to 48 hours after alcohol cessation, although seizures can occur as early as 24 hours or as late as 2 weeks after cessation of alcohol (Victor, 1983) (Box 49-4). Seizures may occur even later with concomitant benzodiazepine abuse. Withdrawal seizures are typically generalized, grand mal, and self-limited. Rarely, seizures may progress to status epilepticus (<3%). Physical signs include an elevated pulse and BP along with signs of autonomic hyperactivity. Researchers have noted increased levels of catecholamine in the locus ceruleus (brainstem) and abnormalities in the neuroinhibitory hormone γ-aminobutyric acid (Mayo-Smith, 2006).

The revised Clinical Institute Withdrawal Assessment for Alcohol scale, revised (CIWA-Ar) is a validated 10-item assessment tool used to quantify the severity of alcohol withdrawal syndrome and to monitor and medicate patients going through withdrawal (Bayard et al., 2004) (Table 49-1). Patients with moderate withdrawal should receive pharmacotherapy to treat their symptoms and reduce the risk of seizures and DTs during outpatient detoxification. Benzodiazepines are the treatment of choice for alcohol withdrawal, according to U.S. and Scottish guidelines (SIGN, 2003). In healthy people with mild to moderate alcohol withdrawal, carbamazepine has many advantages, making it a first-line treatment for properly selected patients (Asplund et al., 2004).

Table 49-1 Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar)^∗

Patient:__________________________ Date: ________________ Time: _______________ (24 hour clock, midnight = 00:00)
Pulse or heart rate, taken for 1 minute:________ Blood pressure:_________

Nausea and Vomiting	Tactile Disturbances
Ask, “Do you feel sick to your stomach? Have you vomited?” Observation. 0 No nausea and no vomiting 1 Mild nausea with no vomiting 2 3 4 Intermittent nausea with dry heaves5 6 7 Constant nausea, frequent dry heaves, and vomiting	Ask, “Have you any itching, pins and needles sensations, any burning, any numbness, or do you feel bugs crawling on or under your skin?” Observation. 0 None 1 Very mild itching, pins and needles, burning, or numbness 2 Mild itching, pins and needles, burning, or numbness 3 Moderate itching, pins and needles, burning, or numbness 4 Moderately severe hallucinations 5 Severe hallucinations 6 Extremely severe hallucinations 7 Continuous hallucinations
Tremor	Auditory Disturbances
Arms extended and fingers spread apart. Observation. 0 No tremor 1 Not visible, but can be felt fingertip to fingertip 2 3 4 Moderate, with patient’s arms extended 5 6 7 Severe, even with arms not extended	Ask, “Are you more aware of sounds around you? Are they harsh? Do they frighten you? Are you hearing anything that is disturbing to you? Are you hearing things you know are not there?” Observation. 0 Not present 1 Very mild harshness or ability to frighten 2 Mild harshness or ability to frighten 3 Moderate harshness or ability to frighten 4 Moderately severe hallucinations 5 Severe hallucinations 6 Extremely severe hallucinations 7 Continuous hallucinations
Paroxysmal Sweats	Visual Disturbances
Observation. 0 No sweat visible 1 Barely perceptible sweating, palms moist 2 3 4 Beads of sweat obvious on forehead 5 6 7 Drenching sweats	Ask, “Does the light appear to be too bright? Is its color different? Does it hurt your eyes? Are you seeing anything that is disturbing to you? Are you seeing things you know are not there?” Observation. 0 Not present 1 Very mild sensitivity 2 Mild sensitivity 3 Moderate sensitivity 4 Moderately severe hallucinations 5 Severe hallucinations 6 Extremely severe hallucinations 7 Continuous hallucinations
Anxiety	Headache, Fullness in Head
Ask, “Do you feel nervous?” Observation. 0 No anxiety, at ease 1 Mild anxious 2 3 4 Moderately anxious, or guarded, so anxiety is inferred 5 6 7 Equivalent to acute panic states, as seen in severe delirium or acute schizophrenic reactions	Ask, “Does your head feel different? Does it feel like there is a band around your head?” Do not rate for dizziness or lightheadedness. Otherwise, rate severity. 0 Not present 1 Very mild 2 Mild 3 Moderate 4 Moderately severe 5 Severe 6 Very severe 7 Extremely severe
Agitation	Orientation and Clouding of Sensorium
Observation. 0 Normal activity 1 Somewhat more than normal activity 2 3 4 Moderately fidgety and restless 5 6 7 Paces back and forth during most of the interview, or constantly thrashes about	Ask, “What day is this? Where are you? Who am I?” 0 Oriented and can do serial additions 1 Cannot do serial additions or is uncertain about date 2 Disoriented for date by no more than 2 calendar days 3 Disoriented for date by more than 2 calendar days 4 Disoriented for place or person

Total CIWA-Ar Score ______
Rater’s Initials ______

∗ The CIWA-Ar is not copyrighted and may be reproduced freely. This assessment for monitoring withdrawal symptoms requires approximately 5 minutes to administer. The maximum score is 67 (see instrument). Patients scoring less than 10 do not usually need additional medication for withdrawal.

From Sullivan JT, Sykora K, Schneiderman J, et al. Assessment of alcohol withdrawal: the revised Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar). Br J Addict 1989;84:1353-1357.

Major alcohol withdrawal, also known as delirium tremens, occurs in less than 5% of alcoholics in withdrawal. Delirium tremens is usually preceded by minor withdrawal symptoms, although they may appear frankly in a patient with minimal symptomatology. The delirium often begins 3 to 4 days after the last drink and is characterized by a marked change in sensorium with agitation, frank hallucinations, and severe disorientation (Box 49-5). Severe and potentially life-threatening autonomic hyperactivity leads to tachycardia, hypertension, and diaphoresis, frequently with low-grade fever. The severe disorientation may lead to self-injury or harm. Typically, the patient’s actions may be appropriate to the context of the state of disorientation and hallucinosis. The patient’s sleep activity is usually disturbed, along with excessive motor activity. Risk factors for DTs are a high blood alcohol level at the initial evaluation, an alcohol withdrawal seizure early in the withdrawal syndrome, and a previous history of delirium (Victor, 1983). Concomitant infections or additional medical disorders may also predispose to severe alcohol withdrawal. Fever over 101° F (38.3° C) should be evaluated further. Before the treatment of alcohol withdrawal, a complete physical examination should be performed to assess the patient, including analysis for GI blood loss.

Withdrawal Treatment

Treatment of alcohol withdrawal consists of supportive and pharmacologic interventions. Supportive interventions include fostering the patient’s desire for abstinence during the withdrawal process. A calm, quiet environment, reassuring and reorienting the patient if confused, decreases the risk of injury or relapse.

The preferred CNS agents for detoxification are the benzodiazepines, according to U.S. and Scottish guidelines (Asplund et al., 2004; SIGN, 2003) and Cochrane review (Ntais et al., 2005). They provide the best side effect profile and have a better risk/benefit profile than other agents. Benzodiazepines are not likely to be fatal in overdose unless mixed with another central depressant (check the urine toxicology screen). Chlordiazepoxide and diazepam are both effective agents. If liver disease is present, or to treat withdrawal in an older patient, oxazepam or lorazepam may be a safer choice because of shorter half-life. Additionally, beta blockers such as atenolol, 50 to 100 mg/day, may decrease tremulousness and sympathomimetic symptoms if there are no contraindications (Table 49-2). A scheduled regimen of chlordiazepoxide, 100 to 300 mg on day 1, followed by daily 50% dose reductions for 3 to 5 days, rather than “as needed” or on a symptom schedule, provides for a smooth withdrawal. Doses must be held for oversedation or somnolence. Monitoring for oversedation is necessary before each dosing (Sullivan et al., 1989). Aggressive regimens support patient comfort, help maintain compliance, and reduce the risk of seizures and major withdrawal. Outpatient detoxification can be performed; without supervision, however, some risk is present (e.g., seizures, self-injury, overdose), and relapse is likely if further alcohol is available.

Table 49-2 Alcohol Withdrawal: Stages and Treatment Summary

Stage	Intervention	Pharmacology
I. Mild	Be supportive. Contact Alcoholics Anonymous. Provide close follow-up.	Thiamine, 100 mg daily Chlordiazepoxide, 25 mg three times daily if necessary, 3 days only
II. Moderate	Allow brief inpatient visit. Make observations. Check laboratory test results (e.g., magnesium, phosphate, electrolyte, glucose levels).	As above, plus chlordiazepoxide, 100-300 mg/day, 3 days only Atenolol, 50-100 mg/day, 3 days only
III. Severe	Hospitalize in ICU. Delirium tremens, intermediate care. Laboratory tests as above. Monitor fluid status. May need restraint. Monitor for infection. Prevent self-harm.	As above, plus chlordiazepoxide, 100 mg hourly until asleep or subdued, then taper. Antipsychotics: haloperidol, 2-10 mg/day Lorazepam, 1-2 mg intravenously if unable to take orally